Nucleosome assembly dynamics involve spontaneous fluctuations in the handedness of tetrasomes.

Abstract:

:DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length of single DNA molecules, we monitor the real-time loading of tetramers or complete histone octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1). Remarkably, we find that tetrasomes exhibit spontaneous flipping between a preferentially occupied left-handed state (ΔLk = -0.73) and a right-handed state (ΔLk = +1.0), separated by a free energy difference of 2.3 kBT (1.5 kcal/mol). This flipping occurs without concomitant changes in DNA end-to-end length. The application of weak positive torque converts left-handed tetrasomes into right-handed tetrasomes, whereas nucleosomes display more gradual conformational changes. Our findings reveal unexpected dynamical rearrangements of the nucleosomal structure, suggesting that chromatin can serve as a "twist reservoir," offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.

journal_name

Cell Rep

journal_title

Cell reports

authors

Vlijm R,Lee M,Lipfert J,Lusser A,Dekker C,Dekker NH

doi

10.1016/j.celrep.2014.12.022

subject

Has Abstract

pub_date

2015-01-13 00:00:00

pages

216-25

issue

2

issn

2211-1247

pii

S2211-1247(14)01051-1

journal_volume

10

pub_type

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